John Strasswimmer1, Benjamin Latimer2, Steven Ory3. 1. Melanoma and Cutaneous Oncology Program, Lynn Cancer Institute, Boca Raton Regional Hospital, Boca Raton, Florida; Department of Biochemistry, Florida Atlantic University, Boca Raton, Florida; Dermatology Associates of the Palm Beaches, Delray Beach, Florida. Electronic address: strasswimmer@gmail.com. 2. Dermatology Associates of the Palm Beaches, Delray Beach, Florida. 3. IVF Florida, Margate, Florida; Department of Obstetrics and Gynecology, Florida International University, Miami, Florida.
Abstract
OBJECTIVE: To report a novel mechanism suggestive of early ovarian failure secondary to the anti-tumor hedgehog-pathway inhibitor vismodegib. DESIGN: Case report and literature review. SETTING: Academic and private dermatology and fertility practices. PATIENT(S): A 34-year-old nulliparous woman with locally advanced basal cell carcinomas who became amenorrheic while receiving oral therapy with vismodegib. INTERVENTION(S): Physical examination and endocrine evaluation. MAIN OUTCOME MEASURE(S): Elevated follicle-stimulating hormone (FSH) and low estrogen in the setting of a normal anti-Müllerian hormone. RESULT(S): FSH was elevated; estrogen was low. Preantral follicles were detected and anti-Müllerian hormone activity was normal. Menses resumed 5 weeks after cessation of therapy. CONCLUSION(S): Vismodegib, a first-in-class inhibitor of the hedgehog signaling pathway is indicated for advanced basal cell carcinoma and is associated with amenorrhea. The mechanism is unknown; it has some features of ovarian failure but preserves ovarian potential through blockading of FSH-receptor-dependent signal transduction. This effect appears to be rapidly reversible upon cessation of therapy. Vismodegib and related compounds may have potential for a role in intervention for gynecologic and endocrine disorders and in therapy for other issues involving FSH-dependent function.
OBJECTIVE: To report a novel mechanism suggestive of early ovarian failure secondary to the anti-tumor hedgehog-pathway inhibitor vismodegib. DESIGN: Case report and literature review. SETTING: Academic and private dermatology and fertility practices. PATIENT(S): A 34-year-old nulliparous woman with locally advanced basal cell carcinomas who became amenorrheic while receiving oral therapy with vismodegib. INTERVENTION(S): Physical examination and endocrine evaluation. MAIN OUTCOME MEASURE(S): Elevated follicle-stimulating hormone (FSH) and low estrogen in the setting of a normal anti-Müllerian hormone. RESULT(S): FSH was elevated; estrogen was low. Preantral follicles were detected and anti-Müllerian hormone activity was normal. Menses resumed 5 weeks after cessation of therapy. CONCLUSION(S): Vismodegib, a first-in-class inhibitor of the hedgehog signaling pathway is indicated for advanced basal cell carcinoma and is associated with amenorrhea. The mechanism is unknown; it has some features of ovarian failure but preserves ovarian potential through blockading of FSH-receptor-dependent signal transduction. This effect appears to be rapidly reversible upon cessation of therapy. Vismodegib and related compounds may have potential for a role in intervention for gynecologic and endocrine disorders and in therapy for other issues involving FSH-dependent function.
Authors: Anne Lynn S Chang; Sarah T Arron; Michael R Migden; James A Solomon; Simon Yoo; Bann-Mo Day; Edward F McKenna; Aleksandar Sekulic Journal: Orphanet J Rare Dis Date: 2016-09-01 Impact factor: 4.123